Use of a solid-supported coupling reagent for a selective phosphitylation of the primary alcohol of N2-isobutyryl-2′-deoxy or 2′-O-methyl guanosine

We have developed a 5′-regioselective phosphitylation of 3′,5′-OH-guanosine derivatives thanks to a solid-supported coupling reagent with either a standard or a bulky phosphine. A 5′-phosphitylation up to a 95% selectivity was obtained with a quantitative conversion of starting nucleoside. After oxidation into thionophosphotriester or phosphotriester by means of solid-supported oxidizers, the 5′-phosphorylated N2-i-Bu-2′-OMe guanosines were isolated in good yields (70–80%).